LATE-BREAKING NEUROLOGICAL NEWS

Low-dose prednisone did not slow cognitive decline in a population of patients with Alzheimer's disease, according to a study in the February 8 Neurology. The dose (initial dose of 20 mg daily for four weeks tapered to 10 mg daily for one year, followed by gradual withdrawal over 16 weeks) was associated with an increase in severe adverse behavioral and physical events. The authors noted that although much higher doses of prednisone are used to treat inflammatory diseases of the brain such as lupus cerebritis and CNS vasculitis, higher doses may not be tolerated for prolonged treatment.

Stroke units are associated with lower mortality and disability rates at five years than other hospital locations, according to a report in the February 26 British Medical Journal. The authors of the study assessed the outcome of 315 stroke patients randomized during one year to either a nonacute stroke rehabilitation unit (176) or to conventional medical or geriatric wards (139). At five years, 45% of the patients in the stroke unit and 55% in the conventional wards had died; 34% of the patients in the stroke unit and 27% in the conventional wards were disabled; and 12% of the patients in the stroke unit and 8% in conventional wards were in institutional care.

Direct costs attributable to epilepsy are below and indirect costs are above previous estimates, according to a report in the March issue of Epilepsia. Direct treatment-related lifetime costs of all persons in the United States with onset in 1995 are $1.8 billion; however, projected combined direct and indirect (loss of productivity) costs are $11.1 billion. The study of 275 Houston patients and 333 Rochester, Minnesota, patients has indicated that epilepsy is associated with a 34% decline in the average man's expected future productivity and a 25% decline in the average woman's expected future productivity. The authors noted that the estimates of direct costs are conservative, as they are based on treatment patterns of the mid 1990s and exclude new treatment options such as vagus nerve stimulation.

N-methyl-D-aspartate receptor activation and GABAergic inhibition are associated with use-dependent plasticity in the motor cortex, reported researchers in the March 14 Proceedings of the National Academy of Sciences. In their study, the effect of lorazepam, dextromethorphan, and lamotrigine on use-dependent plasticity were tested in subjects who engaged in various thumb movements that were voluntary or evoked by transcranial magnetic stimulation. Dextromethorphan (an N-methyl-D-aspartate receptor blocker) and lorazepam (an allosteric modulator of gamma-aminobutyric acid [GABA] type A receptors) substantially reduced use-dependent plasticity.

Lean, older, hypertensive patients should be monitored for additional risk factors for stroke and mortality, according to an article in the February 28 Archives of Internal Medicine. The authors reported that among 3,975 participants in the Systolic Hypertension in the Elderly Program (SHEP) trial, mortality and stroke rates were highest in the quintile with the lowest body mass index. The authors advised caution in weight loss recommendations for older people who are moderately overweight. Low body weight may be due to poor nutrition and may reduce one's ability to withstand physiologic insult, they noted.

Exposure to sumatriptan was associated with an increased odds ratio of preterm delivery (6.3) and low birth weight (3.3) in a Danish study of 16,078 births. The 34 migraineurs who were treated with sumatriptan during pregnancy were compared with 15,955 healthy controls and 89 migraineurs not treated with sumatriptan during pregnancy. No cases of stillbirths or birth defects were reported. The authors noted, in the January Headache, that while these findings may be due to pharmacotherapeutic exposure, they may also reflect disease severity or other confounding factors.

Zonegran™ (zonisamide) has been approved by the Food and Drug Administration as an adjunctive therapy for the treatment of partial (focal) seizures in adults with epilepsy. Zonisamide, a type-T calcium and sodium channel blocker, has been marketed as Excegran^® since 1989 in Japan, where it has had over a million patient years of exposure. Developed by Dainippon Pharmaceuticals Company Limited of Osaka, Japan, the North American and European sales and marketing rights to Zonegran are held by Elan Pharmaceuticals. This therapy is available in 100 mg capsules.

Dexanabinol, a proprietary cannabinoid, significantly reduced the functional and pathologic brain defects in a recent study of animals with experimental autoimmune encephalomyelitis, the most widely used animal model of multiple sclerosis, according to Pharmos Corporation. Dexanabinol, which is a synthetic cannabinoid, lacks the psychotropic effect of natural cannabis. It inhibits neuroinflammation and blocks cell-death cascades, which are also characteristic of stroke, Parkinson's disease, and neuropathic pain. The recent preclinical study was reported in the Journal of Neuroimmunology.

Exposure to human herpesvirus type 6A (HHV-6A) was associated with increased T-cell proliferation in subjects with multiple sclerosis, in a recent study of T-cell response to HHV-6A, HHV-6B, and HHV-7. According to a report in the March Annals of Neurology, there was no statistical difference in the response of subjects with multiple sclerosis and controls to HHV-6B or HHV-7. However 33.3% of healthy controls and 66.6% of subjects with multiple sclerosis responded to lysate of HHV-6A—infected cells. The authors noted that although this finding supports viral association with multiple sclerosis, further research is needed to determine the effect of genetic, immunologic, and environmental factors on multiple sclerosis pathogenesis.

Intraocular pressure is a poor predictor of intracranial pressure, according to a research letter published in the March 11 Lancet. The correspondents evaluated 31 patients (15 with traumatic brain injury, 10 with subarachnoid hemorrhage, three with hydrocephalus, and three with cerebral tumor) for correlation between intraocular and intracranial pressure. The intraocular pressure of both eyes was measured with a noncontact tonometer (Keeler Pulsair air impulse tonometer), which may be used by those without specialist ophthalmic training. Although pressures were related, intraocular pressure explained on average only 12% of intracranial variability.

The proportions of the left and right inferior parietal lobules (IPLs) are reversed in men with schizophrenia, according to a report in the March American Journal of Psychiatry. While both men and women with schizophrenia have smaller IPLs, the left IPL is significantly smaller than the right IPL in men with schizophrenia (a reversed proportion compared with normal controls). The researchers previously reported that the sizes of the right and left Wernicke's region are also reversed in men with schizophrenia. "Since men and women have different brains, the disease naturally expresses itself differently. Women's brains are apparently better protected from whatever schizophrenia does," said lead researcher Godfrey Pearlson, MD.

The Nogo protein has been identified as the inhibitor of axon regeneration following central nervous system injury, according to a report in the January 27 Nature. The Yale University researchers have localized inhibitory activity to 10% of the entire Nogo protein. This may facilitate the identification and design of inhibitors of NOGO action. "If those inhibitors based on Nogo can be developed, the failure of axon regeneration and functional recovery after many brain and spinal injuries might be reversed," said lead researcher Stephen M. Strittmatter, MD.

Unilateral implantation of embryonic porcine ventral mesencephalic tissue was well tolerated at one year by patients with advanced Parkinson's disease, according to a report in the March 14 Neurology. In addition to the 12 million cells implanted in the striatum, the 12 patients received either cyclosporine immunosuppressive or monoclonal antibody treatment. No serious adverse events were connected to the procedure, and cultures were negative for bacterial, porcine endogenous retroviral, and unknown viral contamination. Patients improved 19%, as measured by the Unified Parkinson's Disease Rating Scale scores during the medication "off" state: three patients improved more than 30%, and two showed improvement in gait.

Polyethylene glycol facilitates the partial recovery of nerve conduction in the crushed spinal columns of guinea pigs, according to a report in the January Federation of American Societies for Experimental Biology Journal. The Purdue University, Indiana, researchers reported that after spinal cord damage, 25 of 47 guinea pigs were treated with polyethylene glycol. Recovery of nerve conduction began within 15 minutes of application and continued for up to one month. While 80% of the polyethylene glycol—treated animals showed some recovery of nerve conduction, none of the controls did. Polyethylene glycol is a water-soluble polymer widely used in medicine and cosmetics.

Ethanol elevates levels of allopregnanolone in the brain, reported University of North Carolina researchers in the March 1 Journal of Neuroscience. Within 20 minutes, the steroid can reach pharmacologically active concentrations that have antianxiety and anticonvulsant effects. Women, who have higher levels of allopregnanolone than men have, are statistically less prone to alcoholism, they said. The researchers suggested that the steroid may be linked to the perception of the "rewarding" effect of alcohol or to the mechanism that tells one, "I've had enough to drink, thank you very much; I feel good."

Duration of cardiopulmonary bypass is a predictor of subsequent cerebral dysfunction, according to a report in the March Stroke. Researchers at Wake Forest University, Winston-Salem, North Carolina, examined brain tissue autopsy specimens from 36 subjects who had undergone cardiopulmonary bypass—assisted cardiac surgery at the institution between 1987 and 1997. They found that embolic load increased 90.5% for every hour of cardiopulmonary bypass surgery. In surviving patients, emboli gradually decrease in size and number over time.

The optimal multivariate logistic regression model for identifying patients with nonepileptic seizure (NES) includes the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), routine electroencephalography (rEEG), and historical data, according to an article in the March Epilepsia. The Portland, Oregon, study found that the accuracy of the multivariate classification was 86%; the accuracy of the univariate MMPI-2 Hy scale, 77%; rEEG, 74%; MMPI-2 Hs scale, 72%; age of first spell, 71%; disability application, 70%; number of years since first spell, 65%; and gender, 54%. The authors noted that a multivariate model may be useful for identifying patients for whom a referral for video-EEG monitoring would be of most use. They added that variables in the model may differ according to NES subgroup.

NR

—Kathryn Blair
Associate Editor

Return to table of contents